Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Skeletal class Ⅱ malocclusion is characterized by maxillary protrusion,mandibular retrognathia,or a combination of both,and often accompanied by vertical dimensional discrepancies;treatment is complex,and combined orthodontic-orthognathic surgery is needed for the adult patients.Clear aligner therapy has gradually been applied in complex orthodontic cases.However,limited cases have been reported domestically and internationally regarding the application of clear aligner therapy combined with orthognathic surgery.This article presented a case of a patient with skeletal class Ⅱ high-angle malocclusion treated with the combined therapy and analyzed the clinical efficacy of the treatment appraoch to provide reference for the clinical practice.Extraction of impacted wisdom teeth 18,28,38,and 48,as well as orthodontic teeth 15,25,34,and 44,was performed in stages before orthodontic treatment.Clear aligner therapy was used for preoperative orthodontics.In sagittal plane,a super-complete class Ⅱ canine and molar relationship and a 13-14 mm overjet of the anterior teeth were established.The maxillary and mandibular arch morphology was matched horizontally.The orthognathic surgery included maxillary LeFort Ⅰ osteotomy,bilateral sagittal split ramus osteotomy(BSSRO)and chinplasty.Fine occlusal adjustment was conducted after operation.After treatment,the skeletal relationship between upper and lower jaw was corrected to normal;subspinale-nasion-supramental angle(ANB)was improved from 12.3° to 4.7°;the patient established the class Ⅰ canine and molar relationship,with normal overjet and overbite;root parallelism was good and there was no obvious root resorption;the facial soft tissue profile was significantly improved,and nasion-subnasale-pogonion angle(N-Sn-Pg)was improved from 143.9° to 162.8°.The curative effect was stable 1 year after operation.Clear aligner therapy can efficiently complete combined orthodontic and orthodontic surgery in the complex cases.Compared with the fixed appliance,it is more beneficial to the patients'need for beauty and the maintenance of periodontal health.

Objective:To discuss the ameliorative effect of total flavonoids from corn silk(TFCS)on kidney injury in the rats with urate nephropathy,and to clarify the possible mechanism.Methods:Sixty male Wistar rats were randomly divided into control group,model group,positive control group[benzbromarone(BZM)group,5 mg·kg-1·d-1],low dose of TFCS group(20 mg·kg-1·d-1),medium dose of TFCS group(40 mg·kg-1·d-1),and high dose of TFCS group(80 mg·kg-1·d-1),and there were 10 rats in each group.Except for control group,the rats in the other groups were administered potassium oxonate(350 mg·kg-1)and adenine(70 mg·kg-1)by gavage for 4 weeks to establish the hyperuricemic nephropthy models.The rats in different doses of TFCS groups were treated with TFCS for 2 weeks.Speckle blood flow imager was used to detect the renal blood perfusion of the rats in various groups and the kidney coefficients of the rats in various groups were caculated;HE staining and Masson staining were used to observe the pathomorphology and fibrosis degrees of kidney tissue of the rats in various groups and enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of uric acid(UA),creatinine(Cr),blood urea nitrogen(BUN),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the serum and levels of β2-microglobulin(β2-MG)and microalbumin(ALB)in the urine of the rats in various groups;Western blotting method was used to detect the expression levels of urate transporter 1(URAT1),glucose transporter 9(GLUT9),and ATP-binding cassette transporter G2(ABCG2)proteins in kidney tissue of the rats in various groups.Results:Compared with control group,the renal blood perfusion volume of the rats in model group was significantly decreased(P<0.01).Compared with model group,the renal blood perfusion volumes of the rats in BZM group and low,medium,and high doses of TFCS groups were significantly increased(P<0.05 or P<0.01).Compared with control group,the kidney weight of the rats in model group was increased,with visible white granular spots on the surface,absence of blood color,and kidney volume was increased.Compared with model group,the kidney volumes of the rats in BZM group and medium and high doses of TFCS groups were decreased,with color tending toward that in control group,and the white granular spots on the surface were significantly reduced.Compared with model group,the kidney coefficients of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).The HE staining results showed there were no abnormalities in kidney tissue structure in control group,while there were a small amount of brown-yellow urate crystal deposition and interstitial connective tissue hyperplasia in model group;compared with model group,the kidney tissue damage and inflammatory infiltration were alleviated to varying degrees in BZM group and different doses of TFCS groups.The Masson staining results revealed no obvious collagen fiber deposition in control group,whereas significant blue collagen fiber deposition in kidney tissue of the rats was found in model group,and the collagen volume fraction(CVF)was increased compared with control group(P<0.01);compared with model group,the CVFs of the rats in BZM group and different doses of TFCS groups were decreased(P<0.01).The ELISA results showed that compared with control group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in model group were increased(P<0.01);compared with model group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).Compared with control group,the levels of β2-MG and ALB in urinary in model group were increased(P<0.01);compared with model group,the levels of β2-MG and ALB in urinary of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in BZM group and model group were increased(P<0.01),while the expression level of ABCG2 protein was decreased(P<0.01).Compared with model group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01),and the expression level of ABCG2 protein was increased(P<0.01).Conclusion:TFCS can significantly alleviate the kidney injury in the rats with urate nephropathy model,and its mechanism may be related to the downregulation of expression of URAT1 and GLUT9 proteins and upregulation of ABCG2 protein expression in kidney tissue.

Knee osteoarthritis exhibits a high prevalence and significantly impacts patients′ quality of life. Although surgical interventions demonstrate definitive efficacy, their acceptance rate remains generally low among patients. While knee braces have been widely adopted internationally, domestic research in this field is still limited. International studies suggest that knee braces can be recommended as an early-stage intervention strategy for knee osteoarthritis. Knee braces encompass diverse designs, each with distinct advantages and limitations. Many researchers are actively refining existing brace technologies, while others are innovating novel biomechanical approaches to develop next-generation knee brace systems. Currently, no standardized treatment protocol exists for the use of knee braces in early-stage knee osteoarthritis. This study summarizes and analyzes the research on the application of knee braces in knee osteoarthritis.

ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

Objective To evaluate the perioperative safety and mid-term outcomes of laparoscopic sacrocolpopexy(LSC)and laparoscopic pectopexy(LP)for pelvic organ prolapse(POP).Methods A retrospective analysis was conducted on 274 POP patients,including 178 who underwent LSC and 96 who underwent LP,between August 2017 and January 2023.The extent of prolapse and anatomical restoration were assessed preoperatively and postoperatively using the Pelvic Organ Prolapse Quantification(POP-Q)system.Quality of life outcomes were evaluated with validated questionnaires,including Pelvic Floor Distress Inventory-short form 20(PFDI-20),Pelvic Floor Impact Questionnaire-short form 7(PFIQ-7),and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12(PISQ-12).Postoperative patient satisfaction was assessed during follow-ups.Postoperative anatomical restoration,perioperative status,and postoperative complications,recurrence,and quality of life were compared between the two groups.Multivariate logistic regression was performed to identify postoperative risk factors for recurrence.Results The operative time in the LSC group was significantly shorter than that in the LP group(P<0.05).Intraoperative blood loss was higher in the LSC group compared to that in the LP group(P<0.05).The LSC group also exhibited higher rates of de novo stress urinary incontinence and constipation(P<0.05).The mean follow-up duration was(35.91±16.90)months.The positions of the indicator points(Aa,Ba,C,Ap,and Bp)in the POP-Q classification after the operation were all better than those before the operation.The PFDI-20 score,PFIQ-7 score,and PISQ-12 score all improved compared to those before the operation(P<0.05).Comparison of preoperative and postoperative PFDI-20,PFIQ-7,and PISQ-12 scores showed no intergroup differences.Compared with the LP group,the LSC group had the lower preoperative POP-Q measurements at points Aa and Ba(P<0.05),but superior postoperative measurements for all the indicator points(Aa,Ba,C,Ap,and Bp)(P<0.05).Recurrence occurred in 28 cases in the LP group and 4 cases in the LSC group,with the LP group presenting a significantly higher anatomical recurrence rate than the LSC group did(31.46%[28/89]vs.2.41%[4/166],P<0.05).The subjective cure rate(100%)and objective cure rate(97.59%)in the LSC group were superior to those in the LP group(88.76%and 68.54%,respectively;P<0.05).The results of the multivariate logistic regression analysis showed that,after adjusting for the confounding factors,including age,gravidity,parity,body mass index,and duration of POP,the risk of recurrence after LSC surgery was 0.044 times that after LP(odds ratio[OR],0.044;95%CI,0.015-0.133;P<0.001).Conclusion Mid-term outcomes of LP with partial cervical preservation appear inferior to those of LSC,with LSC demonstrating superior anatomical restoration and lower rates of anatomical recurrence.However,improvements in sexual function and quality of life are comparable between the two procedures.Further evaluation with larger sample sizes and longer follow-up is warranted to better characterize long-term outcomes.

Objective:To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).Methods:Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT.Results:Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy ( t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy ( t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy ( t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions:Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues.

Prostate cancer (PC) is one of the common malignant tumors among men, and its incidence has been increased in China across these years. Radiotherapy is the mainstay therapy for PC. Due to the special biological characteristics of PC and the development of precision radiotherapy technology, hypofractionated regimens of radiotherapy are progressing rapidly, which has been increasingly applied in clinical practice and extensively studied by more and more researchers. In this review, the biological mechanisms of hypofractionated regimens, related clinical research, and practical applications of hypofractionated radiotherapy (such as definitive radiotherapy, postoperative adjuvant / salvage radiotherapy, oligometastasis radiotherapy, and pelvic lymph node radiotherapy) were summarized and its efficacy and toxicity profiles were analyzed, aiming to provide reference for scientific promotion of short‐course, hypofractionated precision radiotherapy for PC in China.

Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

Objective:To evaluate the accuracy of the oral healthcare information provided by different large language models (LLM) to explore their feasibility and limitations in the application of oral auxiliary, treatment and health consultation.Methods:This study designed eight items comprising 47 questions in total related to the diagnosis and treatment of oral diseases [to assess the performance of LLM as an artificial intelligence (AI) medical assistant], and five items comprising 35 questions in total about oral health consultations (to assess the performance of LLM as a simulated doctor). These questions were answered individually by the five LLM models (Erine Bot, HuatuoGPT, Tongyi Qianwen, iFlytek Spark, ChatGPT). Two attending physicians with more than 5 years of experience independently rated the responses using the 3C criteria (correct, clear, concise), and the consistency between the raters was assessed using the Spearman rank correlation coefficient, and the Kruskal-Wallis test and Dunn post hoc test were used to assess the statistical differences between the models. Additionally, this study used 600 questions from the 2023 dental licensing examination to evaluate the time taken to answer, scores, and accuracy of each model.Results:As an AI medical assistant, LLM can assist doctors in diagnosis and treatment decision-making, with an inter-evaluator Spearman coefficient of 0.505 ( P<0.01). As a simulated doctor, LLM can carry out patient popularization, with an inter-evaluator Spearman coefficient of 0.533 ( P<0.01). The 3C scores of each model as an AI medical assistant and a simulated doctor were respectively: 2.00 (1.00, 3.00) and 2.00 (2.00, 3.00) points of Erine Bot, 1.00 (1.00, 2.00) and 2.00 (1.00, 2.00) points of HuatuoGPT, 2.00 (1.00, 2.00) and 2.00 (1.00, 3.00) points of Tongyi Qianwen, 2.00 (1.00, 2.00) and 2.00 (1.75, 2.25) points of iFlytek Spark, 3.00 (2.00, 3.00) and 3.00 (2.00, 3.00) points of ChatGPT (full score of 4 points). The Kruskal-Wallis test results showed that, as an AI medical assistant or a simulated doctor, there were statistically differences in the 3C scores among the five large language models (all P<0.001). The average score of the 5 LLMs on the dental licensing examination was 370.2, with an accuracy rate of 61.7% (370.2/600) and a time consumption of 94.6 min. Specifically, Erine Bot took 115 min, scored 363 points with an accuracy rate of 60.5% (363/600), HuatuoGPT took 224 min and scored 305 points with an accuracy rate of 50.8% (305/600), Tongyi Qianwen took 43 min, scored 438 points with an accuracy rate of 73.0% (438/600), iFlytek Spark took 32 min, scored 364 points with an accuracy rate of 60.7% (364/600), and ChatGPT took 59 min, scored 381 points with an accuracy rate of 63.5% (381/600). Conclusions:Based on the evaluation of LLM′s dual roles as an AI medical assistant and a simulated doctor, ChatGPT performes the best, with basically correct, clear and concise answers, followed by Erine Bot, Tongyi Qianwen and iFlytek Spark, with HuatuoGPT lagging behind significantly. In the dental licensing examination, all the 4 LLM, except for HuatuoGPT, reach the passing level, and the time consumpution for answering is significantly reduced compared to the 8 h required for the exam regulations in all of the five models. LLM has the feasibility of application in oral auxiliary, treatment and health consultation, and it can help both doctors and patients obtain medical information quickly. Howere, their outputs carry a risk of errors (since the 3C scoring results do not reach the full marks), so prudent judgment should be exercised when using them.